The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice

Abstract

Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, such as whether patients should be monitored for DSA pre- or post-transplantation. Pretransplant screening through SPI has become standard practice and DSA are readily determined in case of suspected rejection. However, DSA monitoring in recipients with stable graft function has not been universally established as standard of care. This may be related to uncertainty regarding the clinical utility of DSA monitoring as a screening tool. This consensus report aims to appraise the clinical utility of DSA monitoring in recipients without overt signs of graft dysfunction, using the Wilson & Junger criteria for assessing the validity of a screening practice. To assess the evidence on DSA monitoring, the European Society for Organ Transplantation (ESOT) convened a dedicated workgroup, comprised of experts in transplantation nephrology and immunology, to review relevant literature. Guidelines and statements were developed during a consensus conference by Delphi methodology that took place in person in November 2022 in Prague. The findings and recommendations of the workgroup on subclinical DSA monitoring are presented in this article.

European Survey on Clinical Practice of Detecting and Treating T-Cell Mediated Kidney Transplant Rejection

“…Our survey illustrates that, in Europe, very few centres use innovative non-invasive markers for kidney transplant rejection, and most rely solely on eGFR/creatinine and proteinuria as clinical indication for performing biopsies, while some also see HLA-DSA occurrence and BKPyV replication in plasma as indications for performing a biopsy [ 24 ]. At time of graft dysfunction, in indication biopsies, borderline changes is routinely treated in Europe by 90% of respondents using high-dose steroids, even slightly higher than the 81% of the respondents in the US survey who treat this entity using high-dose steroids [ 15 ].…”

Multi‐centre analytical performance verification of an IVD assay to quantify donor‐derived cell‐free DNA in solid organ transplant recipients

“…3,4 Consequently, non-invasive approaches offer welcome alternatives for allograft surveillance via the measurement of routine clinical biochemistry biomarkers such as serum creatinine (SC) for kidney or donor-specific antibodies (DSA) for SOT. 5,6 These biomarkers allow routine monitoring, but with limitations; SC levels have low sensitivity and specificity and increase after serious kidney tissue damage, 7 while DSA measurement is challenging and has a poor predictive value. 8 Donor-derived cell-free DNA (dd-cfDNA) in transplant recipients' blood has been proposed as a noninvasive marker for allograft injury to aid in surveillance and rejection risk assessment.…”

“…However, biopsy is highly invasive, expensive, inappropriate for frequent assessment, bears procedure‐related risks and is highly subjective 3,4 . Consequently, non‐invasive approaches offer welcome alternatives for allograft surveillance via the measurement of routine clinical biochemistry biomarkers such as serum creatinine (SC) for kidney or donor‐specific antibodies (DSA) for SOT 5,6 . These biomarkers allow routine monitoring, but with limitations; SC levels have low sensitivity and specificity and increase after serious kidney tissue damage, 7 while DSA measurement is challenging and has a poor predictive value 8 …”